Biochemistry chapters
Fat-soluble vitamins
Vitamins A, D, E and K: how they are absorbed and stored, what each does (vision, calcium balance, antioxidant protection, clotting factor carboxylation), the deficiency diseases (night blindness and xerophthalmia, rickets and osteomalacia, haemolysis and neuropathy, bleeding and haemorrhagic disease of the newborn) and toxicity.
- Fat-soluble vitamins (A, D, E, K) are absorbed with fat (need bile and pancreatic lipase), stored in liver and fat, and can accumulate to toxic levels (A and D); deficiency follows malabsorption (cystic fibrosis, coeliac disease, obstructive jaundice, orlistat).
- Vitamin A (retinal forms rhodopsin for dim-light vision; retinoic acid maintains epithelia): deficiency → night blindness (earliest), Bitot spots, xerophthalmia, keratomalacia (blindness), infections; children in deficient areas receive high-dose supplements every 6 months; excess is teratogenic. Vitamin D: skin (UVB) or diet → 25-hydroxylation in the liver (storage form, measured in blood) → 1α-hydroxylation in the kidney (calcitriol, active; stimulated by PTH) → raises calcium and phosphate absorption; deficiency → rickets (children) and osteomalacia (adults).
- Vitamin E is a membrane antioxidant (deficiency: haemolysis, spinocerebellar ataxia, neuropathy); vitamin K enables γ-carboxylation of factors II, VII, IX, X and proteins C and S (blocked by warfarin); newborns are given vitamin K at birth to prevent haemorrhagic disease of the newborn.
On this page
Overview
The fat-soluble vitamins are A, D, E and K.
- Absorbed with dietary fat in micelles (need bile salts and pancreatic lipase), carried in chylomicrons.
- Stored in the liver and adipose tissue, so deficiency develops slowly and excess can be toxic (especially A and D).
- Malabsorption causes deficiency of all four: cystic fibrosis, coeliac disease, obstructive jaundice, chronic pancreatitis, short bowel, and the drug orlistat.
Vitamin A
Forms and sources
- Retinol (alcohol; transport and storage as retinyl esters in liver stellate (Ito) cells), retinal (aldehyde; vision), retinoic acid (acid; gene expression).
- Animal sources: liver, fish liver oil, eggs, milk, butter.
- Plant sources: β-carotene (provitamin A) in carrots, mangoes, papaya, pumpkin, green leafy vegetables.
Functions
- Vision: 11-cis retinal + opsin = rhodopsin in rods (dim light vision). Light converts 11-cis to all-trans retinal, triggering the nerve signal.
- Epithelial integrity: maintains mucus-secreting epithelium (eye, airways, gut, urinary tract); deficiency causes keratinising squamous metaplasia.
- Immunity: deficiency increases severity of measles and diarrhoea.
- Growth, reproduction, embryonic development.
Deficiency (common in malnourished children)
WHO grading of xerophthalmia (in order):
- Night blindness (XN): the earliest symptom.
- Conjunctival xerosis (X1A) and Bitot spots (X1B): foamy, triangular grey-white patches on the temporal conjunctiva.
- Corneal xerosis (X2).
- Corneal ulceration / keratomalacia (X3): softening and melting of the cornea → permanent blindness.
- Corneal scar (XS); xerophthalmic fundus (XF).
Also: dry, rough skin (follicular hyperkeratosis), recurrent infections, growth failure.
Prevention and treatment: high-dose vitamin A to children 6–59 months in deficient areas (100,000 IU at 6–11 months, 200,000 IU every 4–6 months from 12 months), often given with polio or measles campaigns; vitamin A for children with measles.
Age 12 months and over: 200,000 IU on day 1, day 2 and again 2 weeks later
Age 6–12 months: 100,000 IU on the same schedule
Under 6 months: 50,000 IU
Total for a 2-year-old course: 3 × 200,000 = 600,000 IU
1 IU retinol = 0.3 micrograms
200,000 IU × 0.3 = 60,000 micrograms = 60 mg retinol
Doses follow WHO guidance; check the national programme schedule.
Toxicity (hypervitaminosis A)
- Acute: nausea, vomiting, headache, raised intracranial pressure (bulging fontanelle in infants), blurred vision.
- Chronic: dry skin, hair loss, bone pain, liver damage, hypercalcaemia.
- Teratogenic: craniofacial, heart and CNS defects. Isotretinoin (acne) requires strict contraception; high-dose vitamin A supplements are avoided in pregnancy.
Vitamin D
Synthesis and activation
- Skin: 7-dehydrocholesterol + UVB → cholecalciferol (D3). Diet: D3 (fish oils, egg yolk, fortified foods) and ergocalciferol (D2) (plants, fungi).
- Liver: 25-hydroxylation → 25-hydroxyvitamin D (calcidiol): the main circulating and storage form; measured to assess vitamin D status.
- Kidney (proximal tubule): 1α-hydroxylation → 1,25-dihydroxyvitamin D (calcitriol): the active hormone. 1α-hydroxylase is stimulated by PTH, low phosphate and low calcium; inhibited by FGF-23 and high calcitriol.
Actions of calcitriol
- Intestine: ↑ absorption of calcium (calbindin) and phosphate (the main action).
- Bone: mineralisation; with PTH, mobilises calcium from bone.
- Kidney: ↑ calcium and phosphate reabsorption.
- Parathyroid: ↓ PTH secretion.
Deficiency
Causes: little sunlight (covered clothing, staying indoors, darker skin, northern latitudes), diet low in vitamin D, malabsorption, liver disease (no 25-hydroxylation), chronic kidney disease (no 1α-hydroxylation: renal osteodystrophy), anticonvulsants (phenytoin, phenobarbitone induce breakdown), rifampicin, inherited defects (vitamin D-dependent rickets).
Rickets (children, before growth plates close): defective mineralisation of growing bone:
- Craniotabes (soft skull, early), delayed fontanelle closure, frontal bossing.
- Rachitic rosary (swollen costochondral junctions), Harrison sulcus, pigeon chest.
- Widened wrists and ankles, bow legs (genu varum) or knock knees.
- Delayed walking, muscle weakness (hypotonia), dental delay, fractures, hypocalcaemic tetany or seizures.
- X-ray: cupping, splaying and fraying of metaphyses.
Osteomalacia (adults): bone pain and tenderness, proximal muscle weakness (waddling gait), Looser zones (pseudofractures).
Labs in nutritional deficiency: low 25-OH vitamin D, calcium low or normal, phosphate low, ALP high, PTH high (secondary hyperparathyroidism).
Toxicity
Usually from excessive supplements: hypercalcaemia (thirst, polyuria, constipation, confusion), kidney stones, metastatic calcification, renal failure. Also seen in granulomatous diseases (sarcoidosis, TB) because macrophages make calcitriol.
Vitamin E
- Tocopherols (α-tocopherol most active); sources: vegetable oils, nuts, seeds, green vegetables.
- Main lipid-soluble antioxidant: protects membrane fatty acids from free radical damage (works with selenium/glutathione peroxidase and vitamin C).
- Deficiency (rare; fat malabsorption, abetalipoproteinaemia, premature infants): haemolytic anaemia (fragile red cells), spinocerebellar degeneration (ataxia, loss of position sense, absent reflexes: similar to B12 deficiency but no megaloblastic anaemia), peripheral neuropathy, retinopathy.
- Toxicity: large doses may increase bleeding with warfarin.
Vitamin K
Forms and sources
- K1 (phylloquinone): green leafy vegetables.
- K2 (menaquinones): made by gut bacteria.
- K3 (menadione): synthetic (can cause haemolysis and kernicterus in neonates; not used).
Function
Cofactor for γ-glutamyl carboxylase, which carboxylates glutamate residues so proteins can bind calcium:
- Clotting factors II (prothrombin), VII, IX and X.
- Anticoagulant proteins C and S.
- Osteocalcin (bone).
Vitamin K is recycled by vitamin K epoxide reductase, which warfarin blocks.
Vitamin K-dependent factors: 2, 7, 9, 10 ("1972": factors 10, 9, 7, 2) plus proteins C and S.
Deficiency
Causes: newborns (little placental transfer, sterile gut, low vitamin K in breast milk), fat malabsorption and obstructive jaundice, prolonged broad-spectrum antibiotics (kill gut bacteria), poor intake, warfarin, liver disease (poor use).
Features: bleeding (bruising, gut bleeding, haematuria); prolonged PT/INR first (factor VII has the shortest half-life), then APTT.
Vitamin K deficiency bleeding (haemorrhagic disease of the newborn):
- Early: first 24 hours (mothers on anticonvulsants, rifampicin, warfarin).
- Classic: days 2–7: gut, umbilical and circumcision bleeding.
- Late: 2–12 weeks, often intracranial haemorrhage, mainly in exclusively breastfed babies who missed prophylaxis.
- Prevention: vitamin K 1 mg IM at birth for all newborns (0.5 mg for preterm babies under about 1.5 kg).
Treatment of warfarin over-anticoagulation: stop warfarin; vitamin K (oral or IV); prothrombin complex concentrate (or fresh frozen plasma) for major bleeding.
Expect: which vitamins are fat-soluble and why malabsorption causes deficiency, vitamin A in vision (rhodopsin), WHO stages of xerophthalmia (night blindness earliest, Bitot spots, keratomalacia), supplementation schedule, teratogenicity, vitamin D activation steps and the form measured, rickets signs and lab findings, osteomalacia, vitamin D toxicity, vitamin E deficiency (haemolysis, ataxia), vitamin K-dependent factors, warfarin mechanism, haemorrhagic disease of the newborn and prophylaxis.
Quick revision
- Fat-soluble A, D, E, K; malabsorption → deficiency; A and D toxic in excess.
- A: rhodopsin; night blindness → Bitot spots → keratomalacia; teratogenic.
- D: skin/diet → liver 25-OH (measured) → kidney 1,25-(OH)₂ (active; PTH).
- Rickets: craniotabes, rosary, wrist widening, bow legs; ↑ ALP, ↑ PTH, ↓ phosphate.
- E: antioxidant; haemolysis, spinocerebellar ataxia.
- K: γ-carboxylation of II, VII, IX, X, proteins C and S; warfarin blocks recycling.
- Newborns: vitamin K 1 mg IM at birth.
Written by The House Job from standard biochemistry references (Lippincott Illustrated Reviews: Biochemistry).
FAQ
What is the earliest sign of vitamin A deficiency?
Night blindness.
Where is vitamin D activated?
It is hydroxylated first in the liver (25-hydroxyvitamin D) and then in the kidney (1,25-dihydroxyvitamin D, the active form).
Which clotting factors need vitamin K?
Factors II, VII, IX and X, as well as proteins C and S.
Why are newborn babies given vitamin K?
They have low stores, little vitamin K in breast milk and no gut bacteria to make it, so an injection at birth prevents vitamin K deficiency bleeding.